Emergencies Dr. Gwynivere Davies MD FRCPC (Hematology) Apr 2019 - PowerPoint PPT Presentation

Hematology/Oncology Emergencies Dr. Gwynivere Davies MD FRCPC (Hematology) Apr 2019 Spring School

Disclosure Slide Sp Speaker: Dr Dr. Gwyn Da Davies Rel elationship ips with ith commercial l in interests: – Grants/Res esearch Support: Novartis, Teva – Spea eakers Bu Bureau/Honoraria: Non one e to o decla eclare – Con Consult lting Fee ees: Non one to o decla eclare – Oth ther: None to o decla eclare

Topics/Objectives Learn how to handle a new acute leukemic Develop an approach to febrile neutropenia Differentiate between causes of severe thrombocytopenia Immune mediated pneumonitis: recognize it and management Review TBRHSc hematology referral service

Case 1: Mr. AL 51M with right 4 th finger cellulitis, pain ER gets baseline labs, starts him on IV antibiotics and D/C Hgb 93, WBC 8.0, platelets 1066, lytes/BUN/creat N Thoughts? His differential comes back Neutrophils 0.08, lymphocytes 1.60, blasts 5.52 They ask him to come back and do cultures, start him on piperacillin-tazobactam What next?

ASH Image Bank.

Acute Leukemia ≥20% blasts in blood or bone marrow Two main types: Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Can be: de novo From prior disease (ie. MPN) From prior therapy (ie. chemotherapy, radiation) Genetic (ie . AML in Down’s syndrome)

≥20% blasts? Manual blast count CBCs are automated, so there will be issues with the Coulter counter reading the smear Manual smear is read by techs, and reviewed by pathologist Flow cytometry Detects proteins on the surface of cells Like a unique fingerprint, detect if cells are clonal and type

Flow cytometry: only for blasts and lymphocytosis

Don’t Panic! Head-to-toe survey Vitals: febrile, BP (infection, bleeding), O2 Mouth: ulcers, thrush, wet purpura, gingival hyperplasia Lymphadenopathy: more common in ALL CV/Respiratory: flow murmur from anemia, respiratory infection Abdomen: splenomegaly Bleeding: CNS, ophthalmic, GI, GU, mucosal membranes, lines, etc. Misc: derm (leukemia cutis, cellulitis), neurologic (headache, bleed, infection), peripheries (DVT, edema), etc. Labs: CBC, INR/PTT/fibrinogen, PB smear, lytes/BUN/creat/LDH/LETs/ext lytes/uric acid

Acute Myeloid Leukemia (AML) More common in adults Certain types associated with coagulopathies Acute promyelocytic leukemia (APL) has the best prognosis, but 80% have some degree of DIC at diagnosis, and 30% early mortality Lower blast counts cause more problems than in ALL Hyperleukocytosis at WBC 100, rather than around 400 in ALL

Initial Management Transfusions: keep Hgb ≥70 g/L, plt ≥ 10 (≥ 20 if febrile) High risk for clots even with thrombocytopenia (most centres only hold DVTp with platelets <30) If WBC >100 and risk for hyperleukocytosis, be VERY judicious with transfusions Different transfusion parameters if active DIC Assess for tumor lysis syndrome (discussed later) Early investigation of infections, early broad spectrum antibiotics If mold exposures, fungal risk: consider caspofungin, voriconazole, posaconazole

Initial Management: hematologic agents Hydroxyurea Slows down the bone marrow, and can prevent adverse outcomes from high WBC but does not cure acute leukemia Main adverse event (AE) is nausea, can worsen other cytopenias Grastofil (generic neupogen): 300 or 480 mcg sc daily No mortality benefit and risk of stimulating blasts in AML Last ditch Hail Mary if in ICU Tranexamic acid: 1.5 g IV/po tid or 1 g IV/po qid or infusion (if VERY bad bleeding) If epistaxis, can squirt 500 mg on 2x2 and stick up their nose If you don’t have platelets, this is your next best option for bleeding

What am I going to offer? AML: Young, fit: 7+3 IV chemotherapy In the hospital for a month minimum while we wait for counts to recover, then do a bone marrow to assess for remission (then there is more chemotherapy or transplant) Elderly: azacitidine (outpatient chemotherapy sc 7 days per month), non curative Transfusions and supportive care ALL: Young, fit: induction chemotherapy (IV, oral, ++LPs with intrathecal chemotherapy) Protocol is >2 years long (and if cannot tolerate, then consider transplant) Transfusions and supportive care, limited non-curative chemotherapy

Back to Mr. AL On piperacillin-tazobactam, remains febrile CRP 204, ESR 119, blood culture/wound culture: Pseudomonas What do you do? Repeat Xray: Focal lucency and soft tissue swelling are seen at the base of the distal thorax of the 4th digit. Lytic cortical changes seen, ?osteomyelitis. No other focal osseous lesions or fractures

Febrile Neutropenia What is febrile neutropenia? Fever: Single oral temperature ≥38.3ºC OR Oral temperature ≥38.0ºC sustained over 1 (to 2) hr Neutropenia Absolute neutrophil count (ANC) of <500 cells/mm 3 (=0.5 x 10 9 /L) OR ANC expected to fall to <500 cells/mm 3 within 48 hrs ANC = (segmented neutrophils x 10 9 /L)+(bands x 10 9 /L) Anyone can become neutropenic! ESMO Febrile Neutropenia Guidelines, 2016. Ann Oncol.

Expert Opin Pharmacother 2011;12:851-63

Febrile Neutropenia 8 cases/1000 patients receiving chemotherapy (higher risk with heme malignancy) 20-30% require in hospital management, in hospital mortality 10% Common: Gram negative/positive bacteremia, pneumonia, typhilitis/enterocolitis Mortality: 18% GN bacteremia, 5% GP bacteremia ESMO Febrile Neutropenia Guidelines, 2016. Ann Oncol.

Febrile Neutropenia Supportive care, early initiation of broad spectrum antibiotics Consider previous bugs and hospital antibiograms (MDR organisms) Drugs: Anti-pseudomonal monotherapy (pip-tazo on our protocol) Vancomycin for GP: instability, pneumonia, persistent + BC for GP, SSTI infection, MRSA Anti-fungals if 3-7 days without response, antivirals if mucositis or HSV infection Measure difference in time to positivity If 2+ hr faster from line, it’s the line! Remove line if: tunnel infection, pocket infection, persistent bacteremia, mycobacteria and candidemia (IDSA: also if S. aureus or Pseudomonas infections) ESMO Febrile Neutropenia Guidelines, 2016. Ann Oncol.

IDSA 2012 Guidelines.

Grastofil? Works synergistically with bone marrow (if given with chemo) Recommended if risk of FN >20% for all planned cycles of treatment 50% effective at reducing FN episodes Secondary prophylaxis: given after 1st episode of FN Dosing: 5 ug/kg/day, usually 24-72 hr after chemo 300 mcg and 480 mcg syringes Expensive and no overall survival benefit AEs: fever, bone pain, increased ALP/LDH, N/V, splenic rupture

Case 2: Mr. IR 67M presents with 20 lb weight loss, drenching sweats, abdominal pain CT shows diffuse lymphadenopathy, concern for malignancy You get his initial labs back What’s going on?

Tumor Lysis Syndrome (TLS) Mainly occurs with: Initiation of chemotherapy in patients with bulky disease Aggressive lymphomas: Burkitt or lymphoblastic lymphoma AML/ALL with high WBC Can occur spontaneously as tumors outgrow their vascular supply and undergo necrosis

Management of TLS Symptoms: depend on the degree of metabolic abnormalities Nausea, vomiting, diarrhea, lethargy, anorexia, lethargy, hematuria, heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, sudden death Predisposition: Pre-treatment hyperuricemia/hyperphosphatemia Pre-existing renal disease or nephrotoxins, oliguria, dehydration Risk assessment, IVF, diuretics prn (will help with hyperK+), labs q6h Prophylaxis with allopurinol, treatment with rasburicase Dialysis indicated if: refractory fluid overload, refractory hyperuricemia, hyperkalemia or hyperphosphatemia, symptomatic hypocalcemia Cardiac monitoring for hyperkalemia

Case 3: Ms. FA 65F with newly diagnosed metastatic breast cancer presents with extensive bruising and gingival bleeding Oozing at the site of venipuncture Describes blind spot in one eye Hgb 75, WBC 10, plt 15, INR 1.6, PTT 44 What other labs would you want? What is your management? Would you transfuse? What would you target?

Di Diagnos osis He Hemoglobin in Pl Platelets INR INR/PTT Fib Fibrinogen He Hemoly lysis is TTP Low Very low-low Normal Normal Present DIC Low Very low-low High Low Present ITP Low-normal Very low-low Normal Normal Absence HIT Low-normal Low Normal Normal Absence

Disseminated Intravascular Coagulopathy (DIC)

Causes of DIC Critically ill patients with underlying disorder: Sepsis/infection (10-20%) Meningococcemia Trauma (10-20%) Malignancy (10-20%) Pregnancy catastrophes: placental abruption, amniotic fluid embolism, acute fatty liver of pregnancy, retained products Poisoning Major hemolytic transfusion reaction Severe HIT ASH SAP, 2016

Supportive Care CBC, INR, PTT, fibrinogen q6h Transfuse cryoprecipitate for fibrinogen >1.0 g/L 10 units cryo (1 pooled unit) Consumptive coagulopathy for all factors, so not ideal for fibrinogen concentrate Transfuse: Hgb ≥70, plt ≥ 10 or ≥ 50 if bleeding If INR ≥ 1.8, can consider FFP Avoid invasive procedures if possible Assess for organ dysfunction

Thrombotic Thrombocytopenic Purpura (TTP) Acquired auto-antibody against the ADAMTS13 protease Accumulation of large von Willebrand factor (vWF) multimers that bind platelets ASH SAP, 2016.